Olfactory receptor (OR) genes compose a family of ~1,300 genes that are expressed in a, seemingly, stochastic and monoallelic fashion in the mouse olfactory epithelium. Each olfactory sensory neuron expresses only one OR gene from the whole repertoire and this singularity is essential for the proper wiring and function of the olfactory system. Here, we present preliminary data that a repressive epigenetic modification, trimethylation of lysine 9 of histone H3, may be responsible for the silencing of all the OR alleles that are not expressed in a sensory neuron. We propose experiments that will monitor the spatial and temporal coordinates of this modification in the olfactory epithelium and will reveal the molecular components that orchestrate it. These experiments are essential for understanding the role of this repressive mechanism in OR choice and will provide targets for future genetic analyses of epigenetic silencing in the nose. PUBLIC HEALTH RELEVANCE: This proposal aims to analyze the epigenetic silencing of olfactory receptor genes during the development of the olfactory epithelium. Olfaction is a primal human sense and understanding the epigenetic regulation of olfactory receptor genes will uncover principles for the generation of mammalian neuronal diversity and function.